Lesion Expansion Research Articles

Fungicidal spectrum and biological properties of a new fungicide, pyriofenone.

Pyriofenone is a new fungicide developed by Ishihara Sangyo Kaisha, Ltd. To determine the fungicidal spectrum of pyriofenone, in vivo pot tests and in vitro mycelial growth-inhibition tests were conducted. Pyriofenone showed excellent activity against wheat and cucumber powdery mildew and moderate efficacy against rice blast in the pot tests. In the mycelial growth-inhibition tests, most fungi were not affected by pyriofenone except for Botrytis cinerea, Helminthosporium sacchari, Pseudocercosporella herpotrichoides, Pyricularia oryzae, Rosellinia necatrix, and Verticillium dahliae. The fungicidal properties of pyriofenone on powdery mildew in cucumber and wheat were evaluated precisely. Pyriofenone exhibited excellent preventive and residual activities. It had high rainfastness in the cucumber leaves against powdery mildew. Pyriofenone also showed inhibitory activity on lesion development upon application until 2 days after inoculation, and the lesion expansion and sporulation of the cucumber powdery mildew fungus were effectively controlled. Furthermore, pyriofenone showed translaminar and vapor activities.

Drug-coated balloon strategy following orbital atherectomy for calcified coronary artery compared with drug-eluting stent: One-year outcomes and optical coherence tomography assessment.

Percutaneous coronary intervention (PCI) for calcified coronary artery remains challenging in the drug-eluting stent (DES) era. While recent studies reported the efficacy of orbital atherectomy (OA) combined with DES for calcified lesion, the effectiveness of drug-coated balloon (DCB) following OA has not been fully elucidated. Between June 2018 and June 2021, 135 patients who received PCI for calcified de novo coronary lesions with OA were enrolled and divided into two groups; OA followed by DCB (n = 43) if the target lesion achieved acceptable preparation, or second- or third-generation DESs (n = 92) if the target lesion showed suboptimal preparation between June 2018 and June 2021. All patients underwent PCI with optical coherence tomography (OCT) imaging. The primary endpoint was 1-year major adverse cardiac event (MACE), that was a composite of cardiac death, nonfatal myocardial infarction, or target lesion revascularization. Mean age was 73 years and 82% was male. In OCT analysis, maximum calcium plaque was thicker (median: 1050 µm [interquartile range (IQR): 945-1175 µm] vs. 960 µm [808-1100 µm], p = 0.017), calcification arc tended to larger (median: 265° [IQR: 209-360°] vs. 222° [162-305°], p = 0.058) in patients with DCB than in DES, and the postprocedure minimum lumen area was smaller in DCB compared with minimum stent area in DES (median: 3.83 mm2 [IQR: 3.30-4.52 mm2 ] vs. 4.86 mm2 [4.05-5.82 mm2 ], p < 0.001). However, 1 year MACE free rate was not significantly different between 2 groups (90.3% in DCB vs. 96.6% in DES, log-rank p = 0.136). In the subgroup analysis of 14 patients who underwent follow-up OCT imaging, late lumen area loss was lower in patients with DCB than DES, despite lower lesion expansion rate in DCB than DES. In calcified coronary artery disease, DCB alone strategy (if acceptable lesion preparation was performed with OA) was feasible compared with DES following OA with respect to 1-year clinical outcomes. Our finding indicated using DCB with OA might be reduce late lumen area loss for severe calcified lesion.

Deep endometriosis muscular infiltration of the bowel wall: correlation between MRI and histopathology

To assess the correlation between magnetic resonance imaging (MRI) and histopathology for predicting muscular infiltration of endometriosis in the bowel wall in patients undergoing colorectal resection.All consecutive patients who underwent colorectal surgery for deep endometriosis (DE) with a preoperative MRI in a single tertiary care referral hospital between 2001 and 2019 were included in a prospective cohort. MRI images were revised by a single blinded radiologist. The MRI results regarding the infiltration depth (serosal, muscular, submucosal, or mucosal) and lesion expansion of DE were compared to histopathology.A total of 84 patients were eligible for evaluation. A sensitivity of 89% and positive predictive value of 97% was shown for predicting muscular involvement of the bowel wall.This study showed that MRI is valuable in predicting the involvement of the muscular layer of the colorectal wall. Therefore, in patients with symptomatic pelvic bowel endometriosis MRI is a useful tool in guiding the extent of colorectal surgery.

Single Cerebral Metastasis Mimicking Pyogenic Abscess in a Patient with Lung Adenocarcinoma.

HomeRadiology: Imaging CancerVol. 5, No. 3 Images in CancerFree AccessSingle Cerebral Metastasis Mimicking Pyogenic Abscess in a Patient with Lung AdenocarcinomaVíctor Pérez-Riverola , Olalla Vázquez Muiños, Mario Prenafeta Moreno, Roser Monmany Badia, Khalid El-Hamshari Rebollo, Esther Granell MorenoVíctor Pérez-Riverola , Olalla Vázquez Muiños, Mario Prenafeta Moreno, Roser Monmany Badia, Khalid El-Hamshari Rebollo, Esther Granell MorenoAuthor AffiliationsFrom the Department of Neuroradiology, UDIAT-CD, Hospital Universitari Parc Taulí, Parc del Taulí 1, 08208 Sabadell, Spain.Address correspondence to V.P.R. (email: [email protected]).Víctor Pérez-Riverola Olalla Vázquez MuiñosMario Prenafeta MorenoRoser Monmany BadiaKhalid El-Hamshari RebolloEsther Granell MorenoPublished Online:Apr 7 2023https://doi.org/10.1148/rycan.230004MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In As clinical signs of infection are often absent in patients with pyogenic abscesses, differential diagnosis with cerebral metastases is based on MRI findings.However, both entities often manifest as ring-enhancing lesions. Pyogenic brain abscesses usually show restricted diffusion in the lesion core and the dual-rim sign at susceptibility-weighted imaging. The dual-rim sign consists of two concentric rims bordering the lesion: a complete, smooth outer hypointense rim representing the fibrocollagenous capsular wall and an inner hyperintense rim representing a zone of granulation tissue (1). At perfusion imaging, the capsule of a cerebral abscess has a lower relative cerebral blood volume than the necrotic or cystic peripheral wall of a tumor due to microvessel angiogenesis by the tumor (2).Some cerebral metastases also show restricted diffusion, which does not correlate with the histologic type of the primary cancer (3). Proposed mechanisms for restricted diffusion in metastases include intracellular edema in viable tumor cells during transition to complete liquefactive necrosis (4) and a highly viscous mucin concentration (5).Key findings that help distinguish these atypical metastases from pyogenic abscess include high peripheral wall relative cerebral blood volume and absence of the dual-rim sign (Figure).Brain MR images in a 37-year-old male patient, a heavy tobacco and cannabis smoker, after a first seizure. (A) Contrast-enhanced T1-weighted MR image shows a smooth, ring-enhancing nodular right frontal lobe lesion surrounded by abundant vasogenic edema. (B, C) On diffusion-weighted images, the central core shows restricted diffusion. (D) On susceptibility-weighted image, a hypointense smooth ring completely surrounds the lesion, simulating a capsule. (E) The relative cerebral blood volume of the lesion’s peripheral wall (arrows) is high (mean relative cerebral blood volume ratio: 7.61 ± 2.70 [SD]). Chest CT findings (not shown) detected a cavitary pulmonary mass. Tests for tuberculosis and bronchoalveolar lavage fluid analysis were negative. Chest CT findings were initially misinterpreted as an infectious process. Follow-up brain MRI 8 weeks after starting antibiotics showed enlargement of the frontal lobe lesion, new ring-enhancing cerebral and cerebellar lesions, and signs of leptomeningeal carcinomatosis in the posterior fossa. The patient was diagnosed with lung adenocarcinoma following lung lesion biopsy.Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: V.P.R. No relevant relationships. O.V.M. No relevant relationships. M.P.M. No relevant relationships. R.M.B. No relevant relationships. K.E.H.R. No relevant relationships. E.G.M. No relevant relationships.Keywords: MRI, MR-Diffusion-weighted Imaging, MR-Perfusion, Metastasis, Neuro-oncology, Lung Adenocarcinoma, Pyogenic AbscessAuthors declared no funding for this work.

ANNULAR SKIN TUMORS AND LYMPHOPROLIFERATIVE DISEASES.

Determining the shape of the skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area, or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign or malignant skin tumors and lymphoproliferative diseases forming an annular shape.

Chitooligosaccharide accelerated wound healing in potato tubers by promoting the deposition of suberin polyphenols and lignin at wounds

Chitooligosaccharide (COS) is a low molecular weight product of chitosan degradation. Although COS induces plant resistance by activating phenylpropanoid metabolism, there are few reports on whether COS accelerates wound healing in potato tubers by promoting the deposition of phenolic acids and lignin monomers at wounds. The results showed that COS activated phenylalanine ammonialyase and cinnamate 4-hydroxylase and promoted the synthesis of cinnamic, caffeic, p-coumaric, ferulic acids, total phenolics and flavonoids. COS activated 4-coumaric acid coenzyme A ligase and cinnamyl alcohol dehydrogenase and promoted the synthesis of sinapyl, coniferyl and cinnamyl alcohols. COS also increased H2O2 levels and peroxidase activity and accelerated the deposition of suberin polyphenols and lignin on wounds. In addition, COS reduced weight loss and inhibited lesion expansion in tubers inoculated with Fusarium sulfureum. Taken together, COS accelerated wound healing in potato tubers by inducing phenylpropanoid metabolism and accelerating the deposition of suberin polyphenols and lignin at wounds.

Scanning ion conductance microscopy reveals differential effect of PM2.5 exposure on A549 lung epithelial and SH-SY5Y neuroblastoma cell membranes.

Numerous studies have linked a wide range of diseases including respiratory illnesses to harmful particulate matter (PM) emissions indoors and outdoors, such as incense PM and industrial PM. Because of their ability to penetrate the lower respiratory tract and the circulatory system, fine particles with diameters of 2.5µm or less (PM2.5) are believed to be more hazardous than larger PMs. Despite the enormous number of studies focusing on the intracellular processes associated with PM2.5 exposure, there have been limited reports studying the biophysical properties of cell membranes, such as nanoscale morphological changes induced by PM2.5. Our study assesses the membrane topographical and structural effects of PM2.5 from incense PM2.5 exposure in real time on A549 lung carcinoma epithelial cells and SH-SY5Y neuroblastoma cells that had been fixed to preclude adaptive cell responses. The size distribution and mechanical properties of the PM2.5 sample were characterized with atomic force microscopy (AFM). Nanoscale morphological monitoring of the cell membranes utilizing scanning ion conductance microscopy (SICM) indicated statistically significant increasing membrane roughness at A549 cells at half an hour of exposure and visible damage at 4h of exposure. In contrast, no significant increase in roughness was observed on SH-SY5Y cells after half an hour of PM2.5 exposure, although continued exposure to PM2.5 for up to 4h affected an expansion of lesions already present before exposure commenced. These findings suggest that A549 cell membranes are more susceptible to structural damage by PM2.5 compared to SH-SY5Y cell membranes, corroborating more enhanced susceptibility of airway epithelial cells to exposure to PM2.5 than neuronal cells.

Long-term hemodynamic changes in cerebral proliferative angiopathy presenting with intracranial hemorrhage: illustrative case.

Cerebral proliferative angiopathy (CPA) is a rare vascular proliferative disease; however, long-term follow-up reports are scarce. The authors report a rare case and document a patient's medical history over 20 years. A 5-year-old girl developed left frontal lobe hemorrhage, presenting with headache. At 8 years of age, angiography showed diffuse capillary ectasia without an arteriovenous shunt. Single-photon emission computed tomography (SPECT) showed normal cerebral blood flow (CBF). She had normal growth without systemic disease. At 25 years of age, an intraventricular hemorrhage occurred, presenting with sudden headache. Angiography revealed vascular lesion enlargement, increased feeding arteries, dural supply to the nidus and peri-nidal lesion, and flow-related aneurysm. SPECT showed remarkable decreases in CBF in the nidus and peri-nidal lesion. Cerebral proliferative angiopathy (CPA) was diagnosed, and the aneurysm arising at the lateral posterior choroidal artery caused the hemorrhage. Coil embolization of the aneurysm was performed with a flow-guide catheter and extremely soft platinum coils. New aneurysms were not noted 1.5 years after the procedure. This is the first report to demonstrate hemodynamic changes in CPA on angiography and SPECT over 17 years. The development of endovascular devices has enabled the embolization of ruptured aneurysms at the peripheral cerebral artery.

Fungicidal Activity of Novel Quinazolin-6-ylcarboxylates and Mode of Action on Botrytis cinerea.

Fungal diseases remain important causes of crop failure and economic losses. As the resistance toward current selective fungicides becomes increasingly problematic, it is necessary to develop efficient fungicides with novel chemotypes. A series of novel quinazolin-6-ylcarboxylates which combined the structures of pyridine or heterocyclic motif and the N-(3-chloro-4-fluorophenyl)quinazolin-4-amine moiety, a binding group of ATP-binding site of gefitinib, were evaluated for their fungicidal activity on different phytopathogenic fungi. Most of these compounds showed excellent fungicidal activities against Botrytis cinerea and Exserohilum rostratum, especially compound F17 displayed the highest activity with EC50 values as 3.79 μg/mL against B. cinerea and 2.90 μg/mL against E. rostratum, which was similar to or even better than those of the commercial fungicides, such as pyraclostrobin (EC50 , 3.68, 17.38 μg/mL) and hymexazol (EC50 , 4.56, 2.13 μg/mL). Moreover, compound F17 significantly arrested the lesion expansion of B. cinerea infection on tomato detached leaves and strongly suppressed grey mold disease on tomato seedlings in greenhouse. The abilities of compound F17 to induce cell apoptosis of the non-germinated spores, to limit oxalic acid production, to reduce malate dehydrogenase (MDH) expression, and to block the active pocket of MDH protein were demonstrated in B. cinerea. The novel quinazolin-6-ylcarboxylates containing ATP-binding site-directed moiety, especially compound F17, could be developed as a potential fungicidal candidate for further study. This article is protected by copyright. All rights reserved.

PacC mediated ammonia synthesis contributes to the pathogenicity of Trichothecium roseum by regulating reactive oxygen species and extracellular enzymes

The Pal signaling pathway plays an important role in the adaptation of pathogenic fungi to environmental pH fluctuations and consists of PalA, PalB, PalC, PalF, PalI, PalH and Pac C in filamentous fungi. As a key regulator of the Pal signaling pathway, the transcription factor PacC is involved in the regulation of ammonia synthesis, extracellular enzyme activity and pathogenicity of fungi. However, the effect of PacC on the Pal signaling pathway and the production of reactive oxygen species (ROS) in fungi is unknown. It is also unclear whether PacC is involved in the synthesis and transport of ammonia, the alkalinization of environmental pH and the regulation of extracellular enzyme gene expression in Trichothecium roseum. In this study, the wild-type strain, ΔPacC mutant and ΔPacC-C complement strains of T. roseum were used as material to analyze the role of TrPacC in the Pal pathway, ammonia accumulation and environmental pH regulation. Meanwhile, the effect of TrPacC on the pathogenicity of T. roseum was investigated by determining the production of ROS and the expression of extracellular enzyme genes. The results showed that deletion of TrPacC enhanced the pH signal perception and transduction by upregulating the expression of TrPalF and TrPalH, but downregulated the expression of TrPalC, TrPalA and TrPalB, which are involved in PacC activation. Deletion of TrPacC inhibited ammonia synthesis and secretion by downregulating the expression of TrGDH2, TrAMET, TrMEPB and TrGLT1, resulting in reduced ammonia accumulation and attenuated alkalization ability at ambient pH in vivo and in vitro. Deletion of TrPacC also reduced superoxide anion and hydrogen peroxide levels by downregulating TrNoxA expression, but had no significant effect on TrNoxB expression. In addition, deletion of TrPacC downregulated the expression of TrPG, TrPMG, TrPME, TrPL, TrPAL and TrCx and inhibited the lesion expansion of T. roseum on muskmelon and apple fruit. Taken together, deletion of TrPacC attenuated the pathogenicity of T. roseum in muskmelon and apple fruit by reducing the accumulation of ammonia and ROS and inhibiting the expression of extracellular enzyme genes.

Bexarotene improves motor function after spinal cord injury in mice.

Spinal cord injury is a challenge in orthopedics because it causes irreversible damage to the central nervous system. Therefore, early treatment to prevent lesion expansion is crucial for the management of patients with spinal cord injury. Bexarotene, a type of retinoid, exerts therapeutic effects on patients with cutaneous T-cell lymphoma and Parkinson's disease. Bexarotene has been proven to promote autophagy, but it has not been used in the treatment of spinal cord injury. To investigate the effects of bexarotene on spinal cord injury, we established a mouse model of T11-T12 spinal cord contusion and performed daily intraperitoneal injection of bexarotene for 5 consecutive days. We found that bexarotene effectively reduced the deposition of collagen and the number of pathological neurons in the injured spinal cord, increased the number of synapses of nerve cells, reduced oxidative stress, inhibited pyroptosis, promoted the recovery of motor function, and reduced death. Inhibition of autophagy with 3-methyladenine reversed the effects of bexarotene on spinal cord injury. Bexarotene enhanced the nuclear translocation of transcription factor E3, which further activated AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signaling pathways. Intravenous injection of transcription factor E3 shRNA or intraperitoneal injection of compound C, an AMP-activated protein kinase blocker, inhibited the effects of bexarotene. These findings suggest that bexarotene regulates nuclear translocation of transcription factor E3 through the AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signal pathways, promotes autophagy, decreases reactive oxygen species level, inhibits pyroptosis, and improves motor function after spinal cord injury.

Metabolite-Mediated Responses of Phyllosphere Microbiota to Rust Infection in Two Malus Species.

Plants recruit beneficial microbes to enhance their ability to fight pathogens. However, the current understanding of microbial recruitment is largely limited to belowground systems (root exudates and the rhizosphere). It remains unclear whether the changes in leaf metabolites induced by infectious pathogens can actively recruit beneficial microbes to mitigate the growth of foliar pathogens. In this study, we integrated microbiome and metabolomic analyses to systematically explore the dynamics of phyllosphere fungal and bacterial communities and key leaf metabolites in two crabapple species (Malus sp. "Flame" and Malus sp. "Kelsey") at six stages following infection with Gymnosporangium yamadae. Our results showed that the phyllosphere microbiome changed during lesion expansion, as highlighted by a reduction in bacterial alpha-diversity and an increase in fungal alpha-diversity; a decreasing and then an increasing complexity of the microbial co-occurrence network was observed in Kelsey and a decreasing complexity occurred in Flame. In addition, nucleotide sugars, diarylheptanoids, and carboxylic acids with aromatic rings were more abundant in early stages of collection, which positively regulated the abundance of bacterial orders Pseudomonadales (in Kelsey), Acidimicrobiales, Bacillales, and Flavobacteriales (in Flame). In addition, metabolites such as flavonoids, lignin precursors, terpenoids, coumarins, and quaternary ammonium salts enriched with the expansion of lesions had a positive regulatory effect on fungal families Rhynchogastremataceae and Golubeviaceae (in Flame) and the bacterial order Actinomycetales (in Kelsey). Our findings highlight that plants may also influence phyllosphere microorganisms by adjusting leaf metabolites in response to biotic stress. IMPORTANCE Our findings demonstrate the response patterns of bacterial and fungal communities in the Malus phyllosphere to rust fungus G. yamadae infection, and they also reveal how the phyllosphere microbiome changes with the expansion of lesions. We identified several metabolites whose relative abundance varied significantly with lesion expansion. Using a framework for assessing the role of leaf metabolites in shaping the phyllosphere microbiome of the two Malus species, we identified several specific metabolites that have profoundly selective effects on the microbial community. In conclusion, our study provides new evidence of the ecological niche of the phyllosphere in supporting the "cry for help" strategy for plants.

Development and Narrow Validation of Computer Vision Approach to Facilitate Assessment of Change in Pigmented Cutaneous Lesions.

The documentation of the change in the number and appearance of pigmented cutaneous lesions over time is critical to the early detection of skin cancers and may provide preliminary signals of efficacy in early-phase therapeutic prevention trials for melanoma. Despite substantial progress in computer-aided diagnosis of melanoma, automated methods to assess the evolution of lesions are relatively undeveloped. This report describes the development and narrow validation of mathematical algorithms to register nevi between sequential digital photographs of large areas of skin and to align images for improved detection and quantification of changes. Serialposterior truncal photographs from a pre-existing database were processed and analyzed by the software, and the results were evaluated by a panel of clinicians using a separate Extensible Markup Language‒based application. The software had a high sensitivity for the detection of cutaneous lesions as small as 2 mm. The software registered lesions accurately, with occasional errors at the edges of the images. In one pilot study with 17 patients, the use of the software enabled clinicians to identify new and/or enlarged lesions in 3‒11 additional patients versus the unregistered images. Automated quantification of size change performed similarly to that of human raters. These results support the further development and broader validation of this technique.

Abstract P5-13-04: Clonal evolution of mammary epithelial cells into breast cancers

Abstract [Introduction] Proliferative lesions in the breast have been implicated in the development of breast cancer. Previous studies showed that some proliferative lesions and adjacent breast cancers shared common genetic alterations, suggesting that these originated from the same ancestral cell. However, the clonal structure of normal epithelia and their clonal history during evolution to cancer are poorly understood. In this study, we analyzed genetic profiles of normal epithelia and proliferative lesions in the cancer-borne breast to illustrate the clonal evolution of cancer from a normal epithelial cell. [Methods] Single cell-derived organoids (n=47) were established from breast milk of 4 healthy women aged 22–36 and normal breast tissue of 15 breast cancer patients aged 29–83 to evaluate somatic mutation rate in normal epithelial cells. Multiple normal lobules and proliferative lesions together with cancer lesions were collected using laser-capture micro-dissection (LCM) from fresh frozen (n=3) or formalin-fixed paraffin-embedded (n=5) surgical specimens in 9 premenopausal breast cancer patients. Somatic mutations and copy number alterations were evaluated using whole-genome sequencing. [Results] The mutation profile of single cell-derived organoids suggests that somatic mutations accumulate in normal mammary epithelial cells at a constant rate of 19.4/genome/year before menopause, and the mutation rate decreases to 6.9/genome/year after menopause. Parity was negatively associated with mutation number (-49.3 per life birth). In total, we analyzed 143 LCM samples, including those from 72 normal lobules, 43 proliferative lesions, and 19 non-invasive and 9 invasive cancer samples. Five cases showed a large expansion of proliferative lesions sharing a substantial number of somatic mutations with cancer. These lesions expanded over a distance of 35-90 mm, sharing tens to hundreds of mutations including those in breast cancer-related driver genes, such as PIK3CA, AKT1, GATA3, CBFB and PTEN, while harboring private mutations or copy number alterations of their own. Of interest, the cancers in 4 out of these 5 cases was luminal-A type invasive ducal carcinoma or ER-positive HER2-negative ductal carcinoma in situ, and characterized in common by the presence of der(1;16), concurrent whole-arm 1q gain and 16q loss, in both cancer and proliferative lesions. Phylogenetic analysis adapted with the mutation rate in normal cells predicted that der(1;16) had been acquired between puberty and early 20’s, and the common ancestors of non-cancerous and cancerous lesions emerged by early 30’s, &amp;gt;10 years earlier than at the time of cancer diagnosis. By contrast, analysis of non-cancerous lobules unrelated to cancer showed that der(1;16)-negative non-cancer clones that had emerged after puberty stayed within a single lobule or spatially confined to adjacent lobules and rarely expanded to a large area as observed for those carrying der(1;16), even if the clones had acquired mutations in driver genes such as PIK3CA and PIK3R1, which highlighted the role of der(1;16) in wide clonal expansion. [Conclusions] Our results suggest that in some breast cancer cases, particularly in those with der(1;16), a highly recurrent translocation accounting for the major subset of Luminal A breast cancer, the clones with the funder driver alterations expanded macroscopically long before the onset of cancer, in which further clonal evolutions recursively occur multi-focally, giving rise to multiple proliferative lesions and ultimately, invasive cancers. Our findings provide new insight into the early development of breast cancer. Citation Format: Tomomi Nishimura, Nobuyuki Kakiuchi, Kenichi Yoshida, Takaki Sakurai, Tatsuki R. Kataoka, Eiji Kondoh, Yoshitsugu Chigusa, Masahiko Kawai, Morio Sawada, Takuya Inoue, Yasuhide Takeuchi, Hirona Maeda, Satoko Baba, Yusuke Shiozawa, Ryunosuke Saiki, Masahiro M. Nakagawa, Yasuhito Nannya, Yotaro Ochi, Tomonori Hirano, Yukiko Inagaki-Kawata, Kosuke Aoki, Masahiro Hirata, Eiji Suzuki, Masahiro Takada, Masahiro Kawashima, Kosuke Kawaguchi, Kenichi Chiba, Yuichi Shiraishi, Junko Takita, Satoru Miyano, Masaki Mandai, Kengo Takeuchi, Hironori Haga, Masakazu Toi, Seishi Ogawa. Clonal evolution of mammary epithelial cells into breast cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-13-04.

Discrimination between progressive penumbra and benign oligemia of the diffusion-perfusion mismatch region by amide proton transfer-weighted imaging

PurposeAmide proton transfer-weighted (APTw) imaging was an effective tool to reveal the tissue acidosis of acute ischemic stroke. This study aimed to evaluate the ability of APTw MRI to distinguish progressive penumbra and benign oligemia in the diffusion-perfusion mismatch region. Materials and methods38 acute cerebral infarction patients who underwent a comprehensive MRI examination, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), APT imaging, and a follow-up scan in one week were recruited. There were 12 DWI/PWI match cases. The DWI/PWI mismatch patients were divided into 10 progressive cases and 16 stable cases according to the lesion size on the follow-up DWI image compared to the admission scan. Three ROIs: infarction lesion, peripheral, and contralateral normal regions were measured on each subject's MTRasym map. The Friedman test was used to compare the changes of MTRasym among three different regions within each group. The Kruskal-Wallis ANOVA test was used to compare them among the same region of different groups. The correlation between the MTRasym of the peripheral region and the lesion enlargement was analyzed by the Spearman test. ResultsThe MTRasym at the infarction lesion of all three groups showed significant decrease to the contralateral normal tissue. In the progressive mismatch group, the MTRasym at the peripheral region within the DWI/PWI mismatch showed a significant difference with the contralateral normal region and no difference with the infarct core. Whereas both the MTRasym at the peripheral region of the stable mismatch and match groups had no significant difference with the contralateral side, but the differences were significant from those of the central core. When comparing the peripheral region of three groups, the MTRasym of the progressive mismatch group showed a significant decrease to that of the stable mismatch and match groups. The MTRasym of the peripheral region showed a negative correlation with lesion enlargement. ConclusionAPTw imaging is promising to stratify the heterogeneous PWI/DWI mismatch region and benefit the clinical treatment.

Wilms Tumor 1-Driven Fibroblast Activation and Subpleural Thickening in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that is often fatal due to the formation of irreversible scar tissue in the distal areas of the lung. Although the pathological and radiological features of IPF lungs are well defined, the lack of insight into the fibrogenic role of fibroblasts that accumulate in distinct anatomical regions of the lungs is a critical knowledge gap. Fibrotic lesions have been shown to originate in the subpleural areas and extend into the lung parenchyma through processes of dysregulated fibroproliferation, migration, fibroblast-to-myofibroblast transformation, and extracellular matrix production. Identifying the molecular targets underlying subpleural thickening at the early and late stages of fibrosis could facilitate the development of new therapies to attenuate fibroblast activation and improve the survival of patients with IPF. Here, we discuss the key cellular and molecular events that contribute to (myo)fibroblast activation and subpleural thickening in IPF. In particular, we highlight the transcriptional programs involved in mesothelial to mesenchymal transformation and fibroblast dysfunction that can be targeted to alter the course of the progressive expansion of fibrotic lesions in the distal areas of IPF lungs.

Abstract TP95: Utility Of Automated Artificial Intelligence Software In The Analysis Of Ct Perfusion With Acetazolamide Challenge For The Assessment Of Cerebrovascular Reserve In Patients With Cervico-cranial Arterial Stenoses And Occlusions

Background: Cerebrovascular reserve (CVR) assessment is valuable in predicting stroke risk in patients with cranio-cervical stenoses and occlusions. CTP with Acetazolamide challenge (AC) allows a qualitative and quantitative assessment of CVR but is limited by ROI positioning, motion and software. Artificial intelligence (AI) automated software with delay in arrival correction has been validated for the processing of CTP data for acute stroke and may more easily detect abnormal CVR. We sought to compare the results of image-processing with a standard platform (Vitrea™) and AI platform (RAPID™). Methods: Retrospective analysis of an IRB approved prospective database of patients who had CTP with acetazolamide (1g IV) who also had a stenosis/occlusion of the internal carotid or middle cerebral arteries was performed. Symptomatic status was defined as recurrent symptoms related to the vessel of interest within 6 months of scan. Two readers, blinded to the clinical scenario, independently reviewed the CTP datasets and identified CBF regional abnormalities and changes post AC using the 2 different platforms. Abnormal CVR was defined as an increase of CBF post AC of &lt;25% of the baseline in the region of interest with Vitrea™, and an expansion of the volume of tissue with CBF&lt;30% using RAPID™. CTP analyses were correlated with the clinical presentation. Results: Thirty patients fulfilling criteria received CTP before and after AC. 24 patients (80%) were symptomatic. Vitrea™ detected decrease in CBF pre-AC in 27 patients and worsening CBF value post-AC in 19 patients. 10 Patients had an increase &gt;25% in CBF post AC. Rapid™ detected 5 patients with CBF lesion &lt;30% pre-AC. Expansion of the CBF lesion occurred in 8 patients post-AC with a mean change in volume of 7.7 ml (P-value=0.002). The sensitivity for the detection of poor CVR in patients with recurrent symptoms was 80% (95% CI 59.30 - 93.17) with Vitrea™ and 45% (95% CI 25.55%-67.18%) with RAPID™. Conclusion: Automated post processing software with delay in arrival correction algorithm is less sensitive to abnormal CVR and has lower correlation with clinical presentation in this small cohort. Further study is warranted to identify thresholds that may better correlate.

Digital Neuropathy by Hypertrophy and Hyperplasia of Pacinian Corpuscle - Usefulness of Microscopic Resection.

We present a patient with Pacinian corpuscle hypertrophy and hyperplasia in the hand and discuss the diagnosis and treatment of this rare condition. A 46-year-old woman presented with radiating pain of the left middle finger. A strong Tinel-like sign was elicited between the index and middle fingers. The patient frequently used mobile phone, with the corner of the phone consistently applying pressure on the palm. The surgery was carried out under the microscope and two enlarged cystic lesions under the epineurium were found in the proper digital nerve. Histologic examination revealed hypertrophied Pacinian corpuscle with normal structure. Postoperatively, her symptoms gradually improved. Preoperative diagnosis of this disease is very difficult. Hand surgeons should keep this disease in mind preoperatively. In our case, we would not have been able to identify multiple hypertrophic Pacinian corpuscles without the microscope. An operating microscope is recommended in a surgery of this nature. Level of Evidence: Level V (Therapeutic).

Abstract 166: Sex Differences In Perihematomal Edema Volume And Outcome After Intracerebral Hemorrhage

Introduction: Hematoma volume predicts poor outcome after intracerebral hemorrhage (ICH), while outcome associations with perihematomal edema (PHE) remain controversial. Prior studies using non-standardized timing of serial CT imaging reported larger ICH and PHE volumes in men than women, but worse outcome in women. Leveraging data from a cohort with early admission and time-locked follow-up imaging, we investigated the role of sex on PHE and outcomes. Methods: We conducted a post hoc analysis of the randomized FAST (Factor VII for Acute-Hemorrhagic Stroke Treatment) trial. Participants underwent CT imaging within 3 hours of symptom onset, and at 24 and 72 hours. Lesion volumes were calculated using computerized planimetric techniques (AnalyzeDirect). Outcomes (modified Rankin Scale, mRS) were assessed at 90 days. Two-way repeated measures ANOVA tested whether changes in lesion volumes were driven by an interaction between sex and time. Multivariable logistic regression tested for associations between PHE and poor outcome (mRS 4-6). Results: Of 842 subjects, 781 with supratentorial ICH (mean age 65 years, 38% women) were included. Men (n=485) compared to women (n=296) had similar mean ICH and PHE volumes at baseline (p=0.063 and p=0.98) but larger ICH and PHE at 24 hours (p=0.002 and p=0.017) and 72 hours (p=0.002 and p=0.003). All volumes varied over CT time points according to sex (Figure 1 A-C, all three ANOVA: p&lt;0.001). Unlike ICH, PHE expanded between 24 and 72 hours (men: 1.5 ml/h, women: 1.6 ml/h). There was no interaction between PHE changes and FAST-treatment-arm (p=0.85). PHE volume, but not sex, was associated with poor outcome at all CT time points (Figure 1D). Conclusions: Men had greater early lesion expansion than women. In both sexes, PHE expanded beyond 24 hours and was associated with poor outcome. While mechanisms explaining sex differences need further investigation, future ICH studies should be carefully adjusted for sex.

Differential Adaptation Has Resulted in Aggressiveness Variation of Calonectria pseudonaviculata on Hosts Buxus, Pachysandra, and Sarcococca.

Calonectria pseudonaviculata (Cps) infects Buxus (boxwood), Pachysandra (pachysandra), and Sarcococca spp. (sweet box); yet, how it adapts to its hosts has been unclear. Here, we performed serial passage experiments with the three hosts and measured Cps changes in three aggressiveness components: infectibility, lesion size, and conidial production. The detached leaves of individual hosts were inoculated with isolates (P0) from the originating host, followed by nine serial inoculations of new leaves of the same host with conidia from the infected leaves of the previous inoculation. All boxwood isolates maintained their capability of infection and lesion expansion through the 10 passages, whereas most non-boxwood isolates lost these abilities during the passages. Isolates from plants of origin (*-P0) and their descendants isolated from passages 5 (*-P5) and 10 (*-P10) were used to evaluate aggressiveness changes on all three hosts with cross-inoculation. While post-passage boxwood isolates gave enlarged lesions on pachysandra, sweet box P5 and pachysandra P10 isolates showed reduced aggressiveness on all hosts. Cps appears to be most adapted to boxwood and less adapted to sweet box and pachysandra. These results suggest speciation of Cps, with its coevolutionary pace with the hosts the fastest with boxwood, intermediate with sweet box, and the slowest with pachysandra.